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The uptake by man of cadmium ingested in crab meat.

Seven male volunteers with normal iron stores ate the brown meat from crabs whose diet had contained radioactive cadmium-115m. Systemic uptake of cadmium by the volunteers, derived from measurements of their residual body radioactivity several weeks after intake, averaged 2.7 +/- 0.9 (se)%, essentially as found by others in studies with extrinsically labelled food.

Adult↗

Combined effects of mining and smoking in the causation of lung carcinoma. A case-control study in northern Sweden.

Within a case-control study of male lung carcinoma in northern Sweden combined effects of underground mining (iron ore mines) and smoking were analysed. A synergistic effect was found approximately of multiplicative type. Cases with lung carcinoma exposed to underground mining had a considerably lower average cumulative tobacco consumption than other lung carcinoma cases as an expression of the fact that smoking is particularly dangerous in underground miners. Small cell undifferentiated carcinoma was overrepresented among the cases exposed to underground mining and were especially often low tobacco consumers. In the 2 municipalities where the iron mines were located 74 per cent of the male lung carcinoma incidence could be explained by smoking and 55 per cent by underground mining (etiologic fractions).

Aged↗

A simple assay for determination of iron release from ferritin in neuroblastoma cells.

A commercially available enzyme immunoassay was used to determine ferritin content and subsequently the loading and release of iron from ferritin in neuroblastoma cells. LS cells were incubated with 59Fe for 24 h, lysed, and the cytoplasmic ferritin was bound to monoclonal antibodies coupled to globules. After determination of the ferritin content the same globules with bound radioactive ferritin were measured in a gamma-counter. To illustrate the applicability of this test system, increased iron loading of cellular ferritin could be demonstrated in cycloheximide-treated cells; furthermore, release of iron was documented after incubation of LS cells with a combination of 6-hydroxydopamine and ascorbate. The assay turned out to be a simple method for determination of changes in 59Fe content of ferritin in neuroblastoma cells.

Ascorbic Acid↗

Analysis of body-burden measurements of 137Cs and 40K in a Japanese group over a period of 5 years following the Chernobyl accident.

A selected group of about 20 male researchers at the NIRS that reside in Chiba, Japan, was measured for total body content of radiocesium and 40K every 3 mo from February 1986 to May 1991. A whole-body counter at the NIRS was used to measure their radioactivity in a scanning mode of 5 cm min-1 in a shielded iron room with walls 20 cm in thickness. A maximum radiocesium level of 59 Bq was observed in May 1987. The annual change in the body burden decreased with an apparent half-time of 1.8 y after May 1987. The period of five years was sufficient to eliminate the effects of the accident in this group. Even in the most contaminated period, the dose from radiocesium was below 2 microSv y-1. The cumulative dose for 5 y was estimated to be 5.6 microSv, which is nearly equal to the total dose to the Japanese people caused by the artificial radionuclide fallout for the first year following the accident. It is much smaller than the committed dose of 82 microSv for internally deposited 137Cs resulting from nuclear explosions in 1961 and 1962 and the annual dose of 170 microSv from internal 40K. No detectable health risk was expected for the present group.

Body Burden↗

Women with low iron stores absorb iron from soybeans.

BACKGROUND: Worldwide, 30% of the population, a greater proportion of whom are women and children, is iron deficient. Soybeans are a major source of nonheme iron in many human diets, but information on iron bioavailability is still conflicting. Because much of soybean iron is in ferritin [distinct from the poorly bioavailable iron in cereals resulting from interactions between calcium, Fe(III), phytate, and proteins in the meal], soybeans provide a target for manipulating seed iron composition to achieve increased iron bioavailability. OBJECTIVE: The aim was to reevaluate soybean iron bioavailability. DESIGN: Eighteen women, most with marginal iron deficiency, consumed meals with intrinsically labeled ((55)Fe) soybeans (hydroponically grown and nonnodulating) as soup (n = 11) or muffins (n = 7) and a reference dose of (59)Fe as ferrous sulfate in ascorbate solution. The radioactivity in red cells was measured 14 and 28 d later. RESULTS: The mean (55)Fe absorption from either soup or muffins was 27% and that from the reference dose was 61%. (55)Fe was distributed approximately equally between protein (49.3 +/- 3.0%) and phytate, a contrast with nodulating soybeans likely caused by a high phosphate content in the growth medium. There was an expected inverse correlation (r = -0.793, P < 0.001) between red cell radioactivity and serum ferritin concentration. CONCLUSIONS: These results show that soybeans appear to be a good source of nutritional iron in marginally iron-deficient individuals. More study is needed on the effect of plant nodulation on the form of soybean iron, aimed at enhancing bioavailability to combat iron deficiency in at-risk populations.

Adult↗

Lipid peroxidation stimulated by iron nitrilotriacetate in rat liver.

The complex of ferric iron with nitrilotriacetate (iron-NTA) given i.p. is an unusually potent stimulus for lipid peroxidation (LP) in vivo, as monitored by exhaled alkanes. Localization of 59Fe-labeled NTA radioactivity in mouse liver and accumulation of thiobarbituric acid (TBA)-reacting material in liver after i.p. injection suggested that the effect of i.p. iron-NTA could be primarily hepatic. It was found that 100 microM iron-NTA added to a hepatocyte suspension gassed with air stimulated ethane production (3 +/- 1 pmoles/10(6) cells/min) versus an undetectable control, and at a sensitivity of 0.083 pmole/10(6) cells/min. Under similar conditions, hepatocytes stimulated by iron-NTA generated low level chemiluminescence (CL) in parallel with formation of TBA-reactants; the generation of CL was concentration related. Liver was homogenized and fractionated by ultracentrifugation: iron-NTA stimulated CL in whole liver homogenate as in intact cells. The greater part of this activity localized to the microsomal and mitochondrial fractions where NADH or NADPH was required. Using rat liver microsomes, it was shown that iron-NTA in the presence of NADPH stimulated two phases of CL with an initial phase maximum in 1-2 min (phase 1) which decreased abruptly to be followed by a prolonged rise (phase 2); NADH could replace NADPH. Ferrous iron (as chloride) caused a burst of CL, whereas ferric iron was inactive. However, complex differences exist between CL stimulated by Fe(II) and by iron-NTA in the presence of reducing equivalents. Under conditions resulting in the production of CL, a microsomal system with iron-NTA and reducing equivalent accumulated TBA-reactants in parallel with the stimulated CL and rapid increase in oxygen consumption. Both desferrioxamine and butylated hydroxyanisole were able to strongly inhibit the CL stimulated by iron-NTA. When iron-NTA and iron-ADP were compared in the microsomal system, similar responses were obtained but major differences characterized the effects of these iron chelates on whole cells with the ADP complex being relatively inactive. We conclude that iron-NTA stimulated free radical reactions in liver by undergoing cyclic oxidation and reduction and that these reactions utilized oxygen, generated CL, and formed TBA-reactants and ethane. At a subcellular level, the reactions of iron-NTA resembled those reported for iron-ADP.

Adenosine Diphosphate↗

Function of integrin in duodenal mucosal uptake of iron.

A mechanism for the absorption of inorganic iron in the small intestine is described in which integrins appear to play an important role in the passage of iron across microvillous membranes. Biochemical isolates from microvillous preparations of duodenum from rats dosed with radioiron showed radioactivity concentrated in integrins. The presence of integrins on mucosal surfaces of duodenal cells was confirmed by immunofluorescent microscopy using anti-integrin monoclonal antibodies. Immunoprecipitation methods were used to show that microvillous radioiron was precipitated with anti-integrin antibodies and that mobilferrin, a 56-Kd cytosol iron-binding protein, coprecipitated with integrins. We postulate from these data that the mucosal uptake of iron from the gut lumen is mediated via an integrin-mobilferrin pathway.

Animals↗

Iron uptake by Chinese hamster fibroblasts from human transferrin.

The manner of uptake or iron by Chinese hamster fibroblasts, type DON, from human transferrin was investigated by means of replacement studies, in which the cells that were incubated with 125I-labelled human transferrin were chased with non-radioactive transferrin for only a few minutes. The results did not support the reversible endocytosis hypothesis for the uptake of iron from transferrin. The uptake of iron measured as 59Fe during several cell divisions was found to be a function of time and cell number. It was found that the total uptake of iron in the harvests was directly proportional to the incubation, and that the uptake per 10(6) cells levelled off in the course of time.

Animals↗

Retention of cadmium in cadmium-naive normal and iron-deficient rats as well as in cadmium-induced iron-deficient animals.

The retention of cadmium was investigated in cadmium-naive normal and iron-deficient rats in comparison to rats with cadmium-induced iron deficiency. Rats subchronically (4 weeks) exposed to dietary cadmium (28, 56, 112 ppm Cd and 28 ppm Fe) received a radioactively labeled dose of 2 mumol Cd/kg body wt; acutely (no cadmium exposure with diet) treated rats received doses between 1 and 8 mumol Cd/kg body wt. Two animals of each group received iron (1 mumol/kg as 59FeSO4 in order to monitor iron absorption in parallel. After a period of 4 weeks of feeding a cadmium-fortified diet, the test dose was administered and after a 2-weeks period 109Cd and of 59Fe retention was determined. The results showed in part an unexpected pattern of cadmium retention: subchronic feeding of cadmium induced iron deficiency. This implies an immediate interaction between the two metals with regard to intestinal transfer of iron. The retention of iron was increased in the Cd-induced anemia to the same extent as that in iron deficiency induced by iron restriction. Cadmium retention in iron deficiency induced by iron withdrawal also showed a marked increase, which implies that iron deficiency stimulates the intestinal transfer system for both metals in a similar way. Contrary to this effect, the cadmium retention in cadmium-induced iron deficiency was reduced to about 30% of control values. A self-induced aggravation of the body cadmium burden, as a consequence of the iron deficiency which is known to result from subchronic exposure to feeding of dietary cadmium, was thus excluded.

Anemia, Hypochromic↗

Absorption, excretion, and utilization of an intramuscular iron-poly (sorbitol-gluconic acid) complex, Ferastral.

An iron-poly (sorbitol-gluconic acid) complex (Ferastral) labelled with 59Fe was administered by intramuscular injection to clinically and haematologically normal male volunteers. Urinary excretion of radioactivity was measured for the first 48 hours following injection, and was 2%-10% of the administered dose. Disappearance of radioactivity at the site of injection and accumulation of radioactivity in the liver, spleen, and sacrum were measured by external scintillation counting. Plasma radioactivity was measured at intervals for four days and red cell incorporation of 59Fe reached levels of 29%-57.5%. An unexpected finding was that the highest levels of urinary excretion of radioactivity did not coincide with the highest levels of plasma radioactivity.

Absorption↗

Uptake of ferritin by isolated rat hepatocytes. Effect of metabolic inhibitors and iron.

To further characterize the hepatic endocytic pathway of ferritin, the effects of inhibitors of intracellular dissociation of ligands (monensin 15 microM, chloroquine 400 microM), intracellular proteolysis (leupeptin 100 microM) and iron loading on the endocytosis of 125I-rat liver ferritin were studied in isolated rat hepatocytes. Cell associated radioactivity at 37 degrees C was decreased by 27% with chloroquine and 18% with monensin after 4 h. Cell associated radioactivity increased by 38% with leupeptin at 37 degrees C. Acid soluble radioactivity in the extracellular medium was significantly decreased at 4 h in the leupeptin group, which suggests that leupeptin inhibited the lysosomal degradation of the 125I-ferritin resulting in intracellular accumulation of ligand rather than increased uptake of ferritin. Iron loading of cells (5.4-fold increase in intracellular iron) did not significantly alter the binding or accumulation of 125I-ferritin. The characteristics of the endocytic pathway for ferritin are more similar to the asialoglycoprotein receptor than the transferrin receptor, and the hepatic uptake of ferritin is unaffected in this study by increasing the intracellular iron concentration.

Animals↗

Nutrient deprivation of cultured rat hepatocytes increases the desferrioxamine-available iron pool and augments the sensitivity to hydrogen peroxide.

Primary cultures of rat hepatocytes were subjected to amino acid and serum deprivation for 4 h. This treatment augmented the sensitivity to ensuing hydrogen peroxide exposure for 30 min. The by nutrient deprivation-increased autophagocytosis was confirmed by transmission electron microscopy and uptake of the lysosomotropic weak base acridine orange within the intracellular acidic vacuolar apparatus. The desferrioxamine-available pool of iron increased 2.5-fold during deprivation, compared with control cells. Furthermore, amino acid deprivation increased the cellular protein turnover, measured by radioactive labeling with -3H-Leu. Exposure to 40 microM ascorbic acid specifically decreased the turnover of ferritin, as estimated by enzyme-linked immunosorbent assay, and prevented an increase of the desferrioxamine-available iron pool, resulting in protection against hydrogen peroxide-induced cell killing. Thus, hepatocytes with nutrient deprivation-enhanced autophagocytosis contain a larger pool of catalytically active iron than control cells. This iron pool is mainly derived from the turnover (autophagocytosis) of cytosolic ferritin and is probably situated in the lysosomes. Furthermore, nutrient-deprived cells show augmented sensitivity to hydrogen peroxide-induced oxidative stress, since the enhanced availability of iron in low molecular weight form results in an increased potential of intralysosomal Fenton chemistry, that may cause lysosomal rupture with release of potent hydrolytic enzymes.

Animals↗

Simultaneous reduction of radioactive strontium, caesium and iodine retention by single treatment in rats.

The effect of a mixture of calcium alginate, iron (III) ferrocyanide and potassium iodide added to rat diet on 85Sr, 137Cs and 131I metabolism and health was investigated in female rats after four weeks of treatment. The retention of these radioisotopes was determined in the whole body and critical organs six days after 85 Sr and 137CS and one day after 131I oral administration. The health effect of the mixture was evaluated by measuring body weights, haematological parameters, concentrations of iron, zinc and manganese in the kidneys, liver and femur, bone parameters (femur composition and morphometry) and by a histopathological examination. The mixture reduced 85Sr retention in the femur 11 times, 137Cs retention in the thigh muscle 102 times and 131I retention in the thyroid 134 times. Treated animals were in good health and the only differences found between the control and experimental rats were slightly lower haemoglobin values in the blood and a slightly lower iron concentration in the liver. It is concluded that the mixture was very efficient for decreasing body retention of three important fission products and that it can be used over long periods without causing adverse health effects.

Alginates↗

Characterization of siderophore-mediated iron transport in Geotrichum candidum, a non-siderophore producer.

Geotrichum candidum is capable of utilizing iron from hydroxamate siderophores of different structural classes. The relative rates of iron transport for ferrichrome, ferrichrysin, ferrioxamine B, fusigen, ferrichrome A, rhodotorulic acid, coprogen B, dimerium acid and ferrirhodin were 100%, 98%, 74%, 59%, 49%, 35%, 24%, 12% and 11% respectively. Ferrichrome, ferrichrysine and ferrichrome A inhibited [59Fe]ferrioxamine-B-mediated iron transport by 71%, 68% and 28% respectively when added at equimolar concentrations to the radioactive complex. The inhibitory mechanism of [59Fe]ferrioxamine B uptake by ferrichrome was noncompetitive (Ki 2.4 microM), suggesting that the two siderophores do not share a common transport system. Uptake of [59Fe]ferrichrome, [59Fe]rhodotorulic acid and [59Fe]fusigen was unaffected by competition with the other two siderophores or with ferrioxamine B. Thus, G. candidum may possess independent transport systems for siderophores of different structural classes. The uptake rates of [14C]ferrioxamine B and 67Ga-desferrioxamine B were 30% and 60% respectively, as compared to [59Fe]ferrioxamine B. The specific ferrous chelates, dipyridyl and ferrozine at 6 mM, caused 65% and 35% inhibition of [59Fe]ferrioxamine uptake. From these results we conclude that, although about 70% of the iron is apparently removed from the complex by reduction prior to being transported across the cellular membrane, a significant portion of the chelated ligand may enter the cell intact. The former and latter mechanisms seem not to be mutually exclusive.

Biological Transport, Active↗